Overexpression of Batf induces an apoptotic defect and an associated lymphoproliferative disorder in mice

Cell Death Dis. 2012 May 17;3(5):e310. doi: 10.1038/cddis.2012.49.


Activator protein-1 (AP-1) is a dimeric transcription factor composed of the Jun, Fos and Atf families of proteins. Batf is expressed in the immune system and participates in AP-1 dimers that modulate gene expression in response to a variety of stimuli. Transgenic (Tg) mice overexpressing human BATF in T cells were generated using the human CD2 promoter (CD2-HA (hemagglutinin antigen) - BATF). By 1 year of age, over 90% of the mice developed a lymphoproliferative disorder (LPD). The enlarged lymph nodes characteristic of this LPD contain a polyclonal accumulation of T cells with a CD4(+) bias, yet efforts to propagate these tumor cells in vitro demonstrate that they do not proliferate as well as wild-type CD4(+) T cells. Instead, the accumulation of these cells is likely due to an apoptotic defect as CD2-HA-BATF Tg T cells challenged by trophic factor withdrawal in vitro resist apoptosis and display a pro-survival pattern of Bcl-2 family protein expression. As elevated levels of Batf expression are a feature of lymphoid tumors in both humans and mice, these observations support the use of CD2-HA-BATF mice as a model for investigating the molecular details of apoptotic dysregulation in LPD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • CD2 Antigens / genetics
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Hemagglutinins / genetics
  • Hemagglutinins / metabolism
  • Humans
  • Lymphoproliferative Disorders / metabolism
  • Lymphoproliferative Disorders / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • T-Lymphocytes / metabolism
  • Transcription Factor AP-1 / metabolism


  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • CD2 Antigens
  • Hemagglutinins
  • Proto-Oncogene Proteins c-bcl-2
  • Transcription Factor AP-1
  • Caspase 3